高效液相色谱法同时测定人血清中茶碱与苯巴比妥、苯妥英、卡马西平的含量

本文报道茶碱与苯巴比妥（ＰＢ）、苯妥英（ＤＰＨ）、卡马西平（ＣＢＺ）两类（４种）不同药物血浓度的ＨＰＬＣ同时测定法．采用国产色谱柱ＹＷＧＣ１８（４．６×２５０ｍｍ），检测波长为２５４ｎｍ，流动相为甲醇－水（５０：５０，ｖ／ｖ），流速：１ｍｌ／ｍｉｎ，以４－氨基安替匹林作内标，各药物的平均回收率分别为茶碱９９．０２％，ＰＢ１００．７３％，ＤＰＨ１０１．０％，ＣＢＺ１０１．７７％。对各药血清标准液的峰高比测量的变异系数（ｎ＝１０），分别为茶碱（１０μｇ／ｍｌ）６．３％，ＰＢ（２０μｇ／ｍｌ）６．１％，ＤＰＨ（２０μｇ／ｍｌ）４．０％，ＣＢＺ（１０μｇ／ｍｌ）５．２％。本法具有快速、准确、适用性广的特点，用于治疗药物的监测，效果满意，大大提高了实验室的工作效率。     

高效液相色谱法同时测定人血清中茶碱与苯巴比妥,苯妥英,…

本文报道道茶碱与苯巴比（ＰＢ），苯妥英（ＤＰＨ），卡马西平（ＣＢＺ）两类（４种）不同药物血浓度的ＨＰＬＣ同时测定法。采用国产色谱柱ＹＷＧＣ１８（４．６×２５０ｍｍ），检测波长为２５４ｎｍ，流动相为甲醇－水（５０：５０，Ｖ／Ｖ），流速：１ｍｌ／ｍｉｎ，以４－氨基安替匹林作内标，各药物的平均回收率分别为茶碱９９．０２％，ＰＢ１００．７３％，ＤＰＨ１０１．０％，ＣＢＺ１０１．７７％。对各药血清标准液的峰     

RP－HPLC法测定人血清中卡马西平及其环氧化物

用ＲＰ－ＨＰＬＣ法测定人血清中卡马西平（ＣＢＺ）及活性代谢产物卡马西平１０，１１－环氧化物（ＣＢＺ－Ｅ）的含量。血清样品用乙醚－二氯甲烷（３：１，Ｖ／Ｖ）混合溶剂提取，以硝基安定为内标，乙腈－水（４０：６０，Ｖ／Ｖ）为流动相，流速为１．２０ｍｌ／ｍｉｎ，ＵＶ２１５ｎｍ处测定；ＣＢＺ－Ｅ和ＣＢＺ最低检测浓度分别为５０和６０ｎｇ／ｍｌ；线性范围为０．１～５．０μｇ／ｍｌ和０．２～２０μｇ／ｍｌ；ＲＳＤ在５％以下。应用本法测定了８名癫痫病人单一服用ＣＢＺ治疗血清中ＣＢＺ和ＣＢＺ－Ｅ的浓度。     

RP—HPLC法测定人血清中卡马西平及其环氧化物

用ＲＰ－ＨＰＬＣ法测定人血清中卡马西平（ＣＢＺ）及活性代谢产物卡马西平－１０，１１－环氧化物（ＣＢＺ－Ｅ）的含量。血清样品用乙醚－二甲烷（３：１，Ｖ／Ｖ）为流动相，流速为１．２０ｍｌ／ｍｉｎ，ＵＶ２１５ｎｍ处测定。ＣＢＺ－Ｅ和ＣＢＺ最低检测浓度分别为５０和６０ｎｇ／ｍｌ；线性范围为０．１－５．０μｇ／ｍｌ和０．２－２０μｇ／ｍｌ；ＲＳＤ在５％以下。应用本法测定了８名癫痫病人单一服用ＣＢＺ治疗血清中     

高效液相色谱法测定人体地尔硫及其主要代谢物的药物动力学

用高效液相色谱法（ＨＰＬＣ）测定人血清中地尔硫（ＤＺ）及去乙酰地尔硫（Ｍ１）浓度。以ＳｐｈｅｒｉｓｏｒｂＯＤＳ，５μｍ为层析柱，流动相：甲醇∶乙腈∶水（６０∶１０∶３０），检测波长２３７ｎｍ，以盐酸普罗帕酮为内标。检测范围：ＤＺ为５．４５～２７２．５ｎｇ·ｍｌ－１，Ｍ１为５．８５～２９２．５ｎｇ·ｍｌ－１。最低检测浓度：ＤＺ为２．８７ｎｇ·ｍｌ－１，Ｍ１为１．９９ｎｇ·ｍｌ－１。平均回收率ＤＺ为１０１．８８％，Ｍ１为１０１．７２％，ＲＳＤ均在１２％以内。并对４名受试者口服９０ｍｇ盐酸地尔硫片后，其药时曲线经微机用ＰＫＢＰ－Ｎ１程序拟合，ＤＺ为一房室开放模型，Ｍ１为二房室开放模型，求得ＤＺ和Ｍ１的Ｔ１／２分别为５．６±１．５ｈ和１４±７ｈ。     

HPLC法测定两性霉素B含量

目的：用高效液相色谱法测定两性霉素 Ｂ含量。方法：外标法定量，色谱柱为μ－ Ｂｏｎｄａｐａｋ Ｃ柱（１０μｍ， ３．９ｍｍ × ３００ｍｍ）；流动相为乙腈－磷酸盐缓冲液（ｐＨ６． ２０）（５５： ４５， ｖ／ｖ），其中含 ０．０２ｍｏｌ／Ｌ四丁基溴化铵；流速１．２ｍｌ／ｍｉｎ；检测波长４０５ｎｍ。结果：两性霉素Ｂ浓度在３．０～２１．０μｇ／ｍｌ范围内线性关系良好，其相关系数 ｒ＝ ０．９９９７，本方法的平均回收率为 １０２．９４ ± ２．１７％，日内和日间相对标准偏差分别平均为 ２．８０％和５．２５％。结论：该方法简便、快速、准确、重现性好。     

酶法测定血清总胆汁酸在肝病诊断中的应用

通过对英国ＲＡＮＤＯＸ公司生产的酶法测定总胆汁酸试剂盒临床应用应用的可行性进行评价和测定肝病患者血清ＴＢＡ含量，评价酶法测定血清ＴＢＡ在各种肝病诊断中的应用价值。结果；批内ｃｖ为１．２７％和０．８％，批间ｃｖ２．０９％和１．５０％，回收率为１０１．２％，线性范围０－３００μｍｏｌ／Ｌ。     

柔红霉素-白蛋白交联物逆转多药耐药KB/VCR细胞株对柔红霉素的耐药性

将柔红霉素（Ｄａｕ）与牛血清白蛋白（ＢＳＡ）交联，以克服耐长春新碱（ＶＣＲ）的ＫＢ细胞株（ＫＢ／ＶＣＲ）对Ｄａｕ的耐药性．Ｄａｕ抑制ＫＢ和ＫＢ／ＶＣＲ细胞生长的ＩＣ５０分别为３．３μｇＬ－１和０．２６ｍｇＬ－１．ＫＢ／ＶＣＲ细胞对Ｄａｕ的耐药性是ＫＢ细胞的７９倍．反转录聚合酶链式反应结果显示，ＫＢ／ＶＣＲ细胞有很高水平的ｍｄｒ－１基因表达．Ｄａｕ－ＢＳＡ交联物和Ｄａｕ杀伤ＫＢ／ＶＣＲ细胞的ＥＣ５０分别是１２μｇＬ－１（指其中Ｄａｕ含量）和０．２４ｍｇＬ－１，即Ｄａｕ－ＢＳＡ对ＫＢ／ＶＣＲ细胞的细胞毒作用是Ｄａｕ的２０倍．药物蓄积实验显示，使用Ｄａｕ－ＢＳＡ时，ＫＢ／ＶＣＲ细胞内Ｄａｕ蓄积量较使用Ｄａｕ者增加１．４倍（２４ｈ时）；药物外排实验显示，加入Ｄａｕ时，Ｄａｕ迅速从ＫＢ／ＶＣＲ细胞排出，而使用Ｄａｕ－ＢＳＡ时Ｄａｕ能在ＫＢ／ＶＣＲ细胞内长时间维持较高浓度．结果提示，Ｄａｕ与ＢＳＡ交联后，能克服多药耐药细胞对Ｄａｕ的耐药性．     

5—单硝酸异山梨醌制剂溶出度的研究

对５－单硝酸异山梨酯两种市售制剂的溶出度进行ＲＰ－ＨＰＬＣ外标法测定。流动相为甲醇－水，检测波长２２０ｎｍ，线性范围２－８０μｇ／ｍｌ，最低检测浓度０．１μｇ／ｍｌ，ＲＳＤ小于１％。经非线性回归，证实缓释制剂的释药符合一级方程Ｄｔ＝Ｄｍａｘ「７０％（１－ｅ＾－ｋ（ｔ＝ｔ０））＋３０％」。     

Rp－HPLC法测定血清中的抗生育甾体药物利洛司酮

以ＲＵ４８６为内标，建立了血清样品中新型抗孕激素甾体药物利洛司酮（ｌｉｌｏｐｒｉｓｔｏｎｅ）的反相高效液相色谱法。色谱分析条件为μＢｏｎｄａｐａｋＣ１８柱１０μｍ，３００ｍｍ×３．９ｍｍＩＤ；流动相为甲醇－二氯甲烷－１０ｍｍｏｌ·Ｌ－１磷酸盐缓冲液（ｐＨ４．０）（６７：５：２８ｖ／ｖ）；紫外检测波长为３０２ｎｍ。利洛司酮的检测限为１ｎｇ（Ｓ／Ｎ≥４：１）。血清样品经二次液一液超声振荡萃取后，得到了较好的净化。血清样品中利洛司酮的方法回收率为１０３．３％，日内精密度及日间精密度平均ＲＳＤ为３．５１％及２．９２％。在浓度为１０～１０００ｎｇ·ｍｌ－１血清范围内呈线性关系。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.